Medical devices for generating heat and methods of treatment using same

ABSTRACT

A device comprising a heat-generating component that comprises an alkali metal is provided. The alkali metal in the presence of water at a point of contact of the device undergoes an exothermic reaction to generate heat in situ. The amount of heat generated is proportional to and/or limited by the amount (or moles) of water at the point of contact, and the heat generated is sufficient to achieve an increase in temperature at the point of contact to achieve a therapeutic or beneficial result. In one embodiment, the device is used for reducing sweat production in a subject suffering from excessive sweating or hyperhidrosis. In other embodiments, the device is used to substantially sterilize a surface or render a surface substantially aseptic.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/176,907, filed Feb. 19, 2015 and of U.S. Provisional Application No.62/259,315, filed Nov. 24, 2015, both incorporated herein by referencein their entirety.

TECHNICAL FIELD

Devices comprising a substrate and an alkali metal for generating heatare described, where heat is produced in situ. Methods for using thedevices in medical and cosmetic situations are described.

BACKGROUND

Devices that rely on an exothermic reaction as a self-contained heatsource are familiar to consumers in the form of, for example, disposablehand and foot warmers. These devices include a reaction mixture thatgenerates heat when water or oxygen is introduced into the reactionmixture. Devices that produce heat are also used in medical situations,such as in the ablation of tissues or cells, to cauterize wounds, and torender various surfaces substantially aseptic. Cauterization is amedical technique used to stop blood flow and help seal the surface of awound. Various conventional devices for carrying out cauterizationinclude electrocauterizers and laser cauterizers that act to destroytissue while rapidly aiding the coagulation of blood vessels which havebeen cut in the wound. These devices do not typically rely on anexothermic chemical reaction as the source of heat.

Heat can also be used to render surfaces aseptic. For example, a varietyof devices and methods have been used to sterilize surgical instruments(such as autoclaves) and other surfaces, such as a patient's skin or asurgeon's hands, and examples of such devices that are non-heat basedinclude antiseptic wipes, antibacterial solutions, etc. Sterilizationtechniques for instruments generally use heat for extended periods oftime as an aid in destroying bacterial and other pathogens on theinstruments. Sterilization techniques for use with human skin or othersurfaces typically rely on a chemical interaction between the materialbeing applied and the pathogens themselves to destroy the pathogens.

Medical systems such as bandages are conventionally used to slowbleeding by providing pressure to a wound and by assisting with theblood's natural coagulation process that involves platelets in the bloodand fibrin. Bandages are also used to help prevent additional bacterialand other harmful materials from entering an open wound. Bandages usedto cover wounds generally include a portion either directly coupled tothe bandage or coupled to the wound through the bandage that is sterile,such as a gauze pad or other sterile structure.

BRIEF SUMMARY

In a first aspect, a device is provided, the device comprising asubstrate having a first surface and a second surface and an alkalimetal in contact with the substrate. The alkali metal is selected fromsodium and potassium and is present in an amount sufficient to generatean amount of heat in situ when the substrate contacts a surface to bringthe alkali metal in contact with water at a point of contact between thealkali metal and the surface.

In one embodiment, the first surface of the substrate is a first planarsurface and the second surface of the substrate is an opposing planarsurface.

In another embodiment, the first planar surface is a contact surface ordistal surface for contact with a surface to receive heat.

In another embodiment, the opposing planar surface is a proximal surfacein which the alkali metal is in contact.

In yet another embodiment, the alkali metal is embedded in or integralwith the substrate.

In still another embodiment, the alkali metal forms a layer on thesubstrate.

In another embodiment, the alkali metal forms a discontinuous layer onthe substrate.

In other embodiments, the alkali metal forms the layer or thediscontinuous layer on the second surface of the substrate.

In still other embodiments, the alkali metal is in contact with aportion of the substrate.

In yet another embodiment, the substrate is a mesh having open regions,also referred to as interstitial regions or open spaces, and the alkalimetal is embedded in a portion of the open regions.

In one embodiment, the amount of heat generated is limited by the amountof or moles of alkali metal.

In another embodiment, the amount of heat generated is limited by theamount of or moles of water at the site of contact.

In yet another embodiment, the amount of heat generated is proportionalto moles of water present at the site of contact.

In still another embodiment, the heat generated is limited by the amountof or moles of water at the site of contact.

In one embodiment, the heat generated is proportional to the amount ofor moles of water at the site of contact.

In another embodiment, the amount of heat is generated in situ at thesite of contact is in proportion to the moles of water present at siteof contact.

In one embodiment, the alkali metal is neat sodium.

In other embodiments, the alkali metal is an alloy of sodium or an alloyof potassium.

In yet another embodiment, the alkali metal is a sodium/potassium alloy

In still another embodiment, the alkali metal is an oxide of potassiumor an oxide of sodium.

In one embodiment, the substrate is a paste.

In another embodiment, the substrate is an anhydrous aluminum containingpaste.

In another embodiment, the substrate is a metal substrate or metal alloysubstrate.

In other embodiments, the metal substrate is a stainless steel mesh.

In other embodiments, the substrate is a woven substrate.

In still other embodiments, the substrate has a water impermeable layer.

In a second aspect, a kit, comprising a device as described herein, awipe comprising a solvent; and instructions for use, is provided.

In one embodiment, the solvent is isopropyl alcohol.

In another embodiment, the kit further comprises a gauze.

In a third aspect, a method for treatment of a condition is provided.The method comprises applying at a site of contact a substratecomprising an amount of an alkali metal selected from sodium andpotassium to generate heat in situ in an amount sufficient to treat thecondition.

In one embodiment, the heat is generated by an exothermic reaction ofthe alkali metal and water in situ at the site of contact.

In one embodiment, the condition is hyperhidrosis. In anotherembodiment, the condition is perceived excessive sweating.

In certain embodiments, the condition is a wound, or the condition is asymptom associated with seasonal allergies or perceived seasonalallergies seasonal allergies. The symptom, in one embodiment, is a runnynose.

In yet another aspect, a method for treatment of excessive sweating isprovided. The method comprises contacting a substrate comprising anamount of an alkali metal selected from sodium and potassium with a siteof contact on skin of a subject to generate heat in situ in an amountsufficient to treat the condition. In one embodiment, the methodcomprises contacting a substrate comprising an amount of an alkali metalselected from sodium and potassium with a site of contact on skin of asubject to generate heat in situ at the site of contact by an exothermicreaction of the alkali metal and water in situ at the site of contact.

In one embodiment, the excessive sweating is associated withhyperhidrosis.

In another embodiment, the condition is moderate to severehyperhidrosis. In one embodiment, the moderate to severe hyperhidrosisis assigned based on the hyperhidrosis disease severity scale.

In one embodiment, the excessive sweating is perceived excessivesweating.

In another embodiment, the subject is a male subject.

In other embodiments, the site of contact is an underarm (axilla). Inother embodiments, the site of contact is on a position on the subjectselected from a palm of a hand, a sole of a foot, a face, a back, achest or an abdomen.

In one embodiment, contacting is done once per week for a period ofabout one month. In other embodiments, contacting is done once per weekfor a period of between about 1 month to about 12 months.

In yet another embodiment, contacting achieves a temporary reduction insweat production, as measured subjectively by the patient or as measuredby an assessment scale or gravimetrically.

In another aspect, a method for treatment of a wound is provided. Themethod comprises contacting a substrate comprising an amount of analkali metal selected from sodium and potassium with a site of contacton skin of a subject to generate heat in situ in an amount sufficient totreat the wound. In one embodiment, contacting comprises contacting asubstrate comprising an amount of an alkali metal selected from sodiumand potassium with a site of contact on skin of a subject to generateheat in situ at the site of contact by an exothermic reaction of thealkali metal and water in situ at the site of contact.

In one embodiment, the wound is a subcutaneous wound associated with asurgical procedure.

In another embodiment, applying cauterizes skin at the point of contactto close/seal the wound.

In yet another embodiment, applying sterilizes the point of contact.

In still another embodiment, uninjured skin adjacent injured/woundedskin exposed to the device is not visually altered by the treatment.

In yet another aspect, a method for attenuation or treatment of asymptom associated with seasonal allergies or with perceived seasonalallergies is provided. The method comprises contacting a substratecomprising an amount of an alkali metal selected from sodium andpotassium with a site of contact in nasal tissue of a subject togenerate heat in situ in an amount sufficient to treat the heat thenasal tissue and attenuate or the symptom. In one embodiment, contactingcomprises contacting a substrate comprising an amount of an alkali metalselected from sodium and potassium with a site of contact in nasaltissue of a subject to generate heat in situ at the site of contact byan exothermic reaction of the alkali metal and water in situ at the siteof contact in an amount sufficient to treat the heat the nasal tissueand attenuate or the symptom.

In one embodiment, the symptom is a runny nose.

In various embodiments of the aspects detailed herein, the amount ofheat generated in situ relates to, is controlled by, is proportional to,and/or is limited by an amount of water at the point of contact.

In another embodiment of the aspects detailed, the oxidizing material isnot Fe, Al, Mg, Zn or C.

In other embodiments of the aspects detailed, the device isnon-invasive.

In other embodiments of the aspects detailed, the alkali metal is not inthe form of particles coated or encapsulated or encased with a polymer

In other embodiments of the aspects detailed, the carrier is non-stickyand cannot and/or does not adhere to a skin surface.

In other embodiments of the aspects detailed, the heat generatedproduces a temperature profile at the point of contact, and thetemperature profile is not constant over any 3 minute interval, 1 minuteinterval, or 2 minute interval, during a period of contact between thesubstrate and the surface.

The foregoing and other aspects, features, and advantages will beapparent to those artisans of ordinary skill in the art from thedescription, drawings and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a photograph of a device according to one embodiment, wherethe device is in the form of a bandage comprising a substrate with acomposition comprising solid sodium metal coupled to the substrate;

FIG. 1B is a photograph of the bandage-like device of FIG. 1A applied toa skin surface, the device applied to that the heat-generating componentcontacts an injured skin region and an intact skin region;

FIG. 1C is a photograph of the uninjured skin region and the woundedskin region, showing a first wound and a second wound, followingapplication of the bandage-like device;

FIG. 1D is a photograph of two portions of the skin of FIG. 1C showing aportion that was uninjured and a portion that was wounded;

FIG. 1E is close up photograph of the two regions of the skinillustrated in FIG. 1D;

FIGS. 1F-1G are photomicrographs of cross sections of the top surfaceportion of the first wound (FIG. 1F) and a second wound (FIG. 1G) in theskin of FIGS. 1C-1E;

FIG. 1H is a photomicrograph of a cross section of a lower portion ofthe wound in the skin illustrated in FIGS. 1C-1E;

FIGS. 1I-1J are photomicrographs of cross sections of two differentregions of the top surface of the uninjured portion of the skinillustrated in FIGS. 1C-1E;

FIGS. 2A-2C are photographs of petri dish streaked with Escherichia colibacteria, the photograph taken immediately after streaking (at anelapsed time equal to 0 hours), where the petri dishes are labelledaccording to treatment to be applied: ‘reference’ (control, untreated(FIG. 2A)), “water” (FIG. 2B) and “water+device” (FIG. 2C);

FIGS. 2D-2F are photographs of the petri dishes 4 hours after streakingwith E. coli and untreated (FIG. 2D), treated with water only (FIG. 2E)and treated with water and a device as described herein (FIG. 2E);

FIGS. 2G-2I are photographs of the petri dishes 24 hours after streakingwith Escherichia coli bacteria and not treated (reference, FIG. 2G),treated with water (FIG. 2H), and treated with a device as describedherein (FIG. 2H);

FIGS. 2J-2L are photographs of the petri dishes 48 hours after beingstreaked with Escherichia coli bacteria and not treated (reference, FIG.2J), treated with water (FIG. 2K), and treated with a device asdescribed herein (FIG. 2L);

FIG. 3A is a photograph of a petri dish containing a growth of bacteriathereon;

FIG. 3B is a photograph of the petri dish of FIG. 3A followingapplication of sodium metal to the surface of the petri dish;

FIG. 4A is a photograph of a male patient with hyperhidrosis treated forstain testing at time equal 0 minutes;

FIG. 4B is a photograph of the same male patient at time equal 5minutes;

FIG. 4C is a photograph of the male patient of FIG. 4A following asingle treatment with NaK in an aluminum salt base and treated for staintesting at time equal 0 minutes;

FIG. 4D is a photograph of the male patient of FIG. 4A at time equal 5minutes post treatment;

FIG. 4E is a photograph of the patient of FIG. 4A at time equal 10minutes post treatment;

FIG. 5A is a photograph of a patient's left axilla treated for staintesting at 90 seconds post testing prior to treatment;

FIG. 5B is a photograph of the left axillia of the patient of FIG. 5Aafter treatment by an oil emulsion including NaK at 90 seconds posttreatment for stain testing;

FIG. 5C is a photograph of the left axillia of the patient of FIG. 5Aafter a second treatment with an oil emulsion including NaK at 90seconds post treatment for stain testing;

FIG. 6A is a photograph of the axilla of a patient after 90 secondsfollowing stain testing; and

FIG. 6B is a photograph of the axilla of the patient of FIG. 6Afollowing treatment with an aluminum salt suspension containing NaK at90 seconds following stain testing.

DETAILED DESCRIPTION

Various aspects now will be described more fully hereinafter. Suchaspects may, however, be embodied in many different forms and should notbe construed as limited to the embodiments set forth herein; rather,these embodiments are provided so that this disclosure will be thoroughand complete, and will fully convey its scope to those skilled in theart.

Where a range of values is provided, it is intended that eachintervening value between the upper and lower limit of that range andany other stated or intervening value in that stated range isencompassed within the disclosure. For example, if a range of 1 μm to 8μm is stated, it is intended that 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, and 7 μmare also explicitly disclosed, as well as the range of values greaterthan or equal to 1 μm and the range of values less than or equal to 8μm.

The singular forms and “the” include plural referents unless the contextclearly dictates otherwise.

I. DEVICES

In one aspect, devices comprising a component for generating heat areprovided. The component that generates heat comprises a substrate and analkali metal. This component of the devices is now described.

The alkali metal is present in the devices in an amount sufficient togenerate heat. As used herein an ‘alkali metal’ intends a univalent(monovalent) metal belonging to group 1A of the periodic table,including potassium, sodium, lithium, rubidium, cesium and francium.Reference to ‘alkali metal’ or to one of the specific metals, e.g.,potassium metal or sodium metal, include its salts, oxides, peroxides,superoxides, hydroxides, halides, and the like, provided the alkalimetal in the presence of water undergoes an exothermic reaction.Reference to an ‘alkali metal’ also includes alloys that comprise one ormore alkali metals.

In one embodiment, the alkali metal is potassium or sodium. In anotherembodiment, the alkali metal is a neat alkali metal, sometimes referredto as the free metal, such as potassium free metal or sodium free metal.In other embodiments, the alkali metal is potassium or sodium in theform of an oxide. Sodium monoxide (Na₂O) and sodium peroxide (Na₂O₂) andsodium superoxide (NaO₂) are examples. Sodium metal is a soft metal thatis highly reactive with oxygen and water. Sodium metal can be cut,broken up, and shaped into various forms due to its softness. Potassiummetal is likewise a soft metal that has higher reactivity with oxygenand water than does sodium metal.

In another embodiment, the alkali metal is an alloy, such as an alloy ofsodium and potassium. Sodium metal and potassium metal can be combinedto form a sodium/potassium alloy (NaK) which is a liquid at roomtemperature. NaK that is liquid at room temperature contains betweenabout 40% to about 90% potassium by weight. A eutectic between sodiumand potassium occurs at about 77% potassium and about 23% sodium and theliquid metal at the eutectic point is less dense than water. Eutecticcompositions may be used in various embodiments of the devices describedherein, as well as any combination of sodium and potassium inproportions that form a stable alloy. Accordingly, the term “NaK” isused herein to refer to a sodium and potassium alloy, as used herein,this term represents any possible combination of sodium and potassiumand not just a 50/50 atomic mixture and not just a eutectic composition.

Sodium metal when contacted by water generates hydrogen gas and heataccording to the following reaction:2Na(s)+2H₂O(l)→2NaOH(l)+H₂(g)+184 kJFor sodium metal 4.0 MJ/kg of Na(s) can be generated directly and 5.3MJ/kg Na(s) is generated from combustion of the hydrogen gas withoxygen. The reaction involves equimolar amounts (that is, equal numbersof atoms or molecules) or the alkali metal (e.g., sodium) and water toform a mole of alkali metal hydroxide and half a mole of hydrogen gasand heat. Accordingly, a large amount of heat from a relatively smallamount of sodium metal is generated. The reaction stops when the alkalimetal (e.g., sodium metal) is fully consumed, thus the amount of heatgenerated can be directly calculated and controlled by the amount ofmetal involved in the reaction. Similar reactions that releaserelatively large amounts of heat also occur for potassium metal and forNaK alloys when contacted with water, and the amount of heat generatedis controllable by the amount of alkali metal and/or by the amount ofwater available for reaction with the alkali metal.

Because of the large amount of heat generated through the reaction ofalkali metals, such as sodium, potassium, and NaK, with water, devicescomprising one or more of these metals can be used in medical andcosmetic procedures where heat provides a beneficial therapy or effect,as will be further described below. The exothermic reaction generates insome cases sodium hydroxide, and a buffering component may optionally beused in conjunction with the alkali metal to neutralize the sodiumhydroxide, causing the effects of the composition to be the result ofheat generation. The heat generated by the alkali metal depends, inpart, upon the amount available for reaction, the amount of water at apoint of contact on a surface available for reaction, and (in somecases) the way in which the alkali metal is contacted with a surface(e.g., wound or skin) for contact with water present at the surface. Thealkali metal may be mixed with other compounds and/or metals to controlthe heat release properties, reactivity, shapeability, or other physicalcharacteristic of the alkali metal, if desired.

In the device, the alkali metal is typically formed on, in contact with,incorporated into, or associated with a base or a substrate. The base orsubstrate is preferably inert and does not contribute to or deter theexothermic reaction that occurs when the alkali metal contacts water.The terms “base” and “substrate” are used interchangeably herein, andthis element of the heating component functions to support and/or carrythe alkali metal. Several non-limiting examples for purposes ofillustration are provided herein, and a wide variety of base designs canbe constructed using the principles disclosed herein.

In one embodiment, the base is a dermal pen or dermal roller, and thealkali metal (e.g., the sodium metal or potassium metal or NaK alloy) isheld within the dermal pen or dermal roller. The dermal pen or dermalroller is then subsequently used to contact the alkali metal with apatient's skin. In another embodiment, the dermal roller is a hotroller, and may be configured for use by a patient on their own or foruse by a doctor or other medical staff in a medical office. In otherembodiments, the base is a bandage and the alkali metal, (e.g., sodiummetal, potassium metal, or NaK) is included in a sterile dressingcoupled to the bandage. In other implementations, the alkali metal(sodium metal, potassium metal, or NaK) is included on the surface ofthe sterile dressing.

In another embodiment, the substrate is a needle, a wipe or a sponge,and devices using these substrates are further described below. Devicesusing a needle contemplate hollow needles and solid needles, where thealkali metal is a coating on the external surface of the needle or, forhollow needles, in the annual space of the needle. Devices using a wipeor a sponge as the substrate contemplate porous and non-porous materialswhere the alkali metal forms a layer on the substrate, is embedded inpores or openings in the substrate, or a combination of both a layer andembedded in pores.

In another embodiment, the substrate is a planar substrate havingopposing sides. That is, the planar substrate has a first side and asecond side. In other embodiment, the substrate has a first side and asecond side, and is non-planar. In embodiments where the substrate has afirst side and a second side, the first side may be referred to as adistal surface or a contact surface. The contact surface intends thesurface of the substrate that contacts a surface to receive heat duringuse of the device, as described below. The second side of the substratemay be referred to as a proximal surface. The proximal surface is incontact with, supports, or carries the alkali metal and/or is in contactwith a backing member on the device if such a member is desired orneeded. The alkali metal on the substrate may cover the entire substrateor may cover a portion of the substrate. The alkali metal on thesubstrate may be a discontinuous layer disposed on or in all or aportion of the substrate, or may be a continuous layer on or within allor a portion of the substrate. In one embodiment, the substrate is awoven material, and in another embodiment it is a non-woven material. Insome of the exemplary embodiments described in the working examplesbelow, the substrate is a mesh, i.e., a material having open regions(interstitial regions or open spaces) in a network of fibers. The alkalimetal is embedded in all or a portion of the open regions of the meshsubstrate.

The material forming the substrate is preferably one that is inert inthe presence of the exothermic reaction and its reactants and is stablein the presence of the heat generated. Non-limiting examples includemetals, such as iron, copper, zinc, nickel, palladium, platinum, gold,titanium. The metal may be treated by painting, anodizing or plating.The substrate may also be a metal alloy, such as alloys of iron (e.g.,steel, stainless steel, cast iron, alloy steel), allows of aluminum,titanium, copper (e.g., bronze) and magnesium. Steel are alloys of ironand other elements, primarily carbon. Stainless steel is a steel alloywith chromium, the latter typically present at a minimum of 10.5 wt % ofthe alloy composition. Other examples of materials for forming thesubstrate include heat resistant fabrics and/or fire retardant fabrics,such as those sold under the tradenames KOVENEX® and NOMEX®. Exemplarymaterials in heat-resistant fabrics include fiberglass, polyesters,imidazole based polymers like polybenzimidazole, aramid based polymerslike polyaramid, amorphous silica cloth, silic cloth with cured siliconrubber on one side, aluminized polyester, composites of polymers andfiberglass (such as a composite of aramid and fiberglass fibers),aluminized cloth, aluminized polyester, cloth of stainless steel wire,cloth of a brass wire plied with fiberglass yarns, and the like.Materials may also be topically treated with a chemical, such as withpolytetrafluoroethylene, to render the material heat resistant or fireretardant.

As mentioned above, the base may take the form of a knife or blade. Inthis embodiment, the alkali metal may be in the form of a coating orlayer on the surface of the knife or blade. Surgical scalpels or knivesare one example, where the alkali metal forms a coating or layer on theedge of the scalpel or knife used to contact the skin, where it isdesirable for the wound being created by the scalpel or knife to becauterized through reaction of the alkali metal coating with the waterin the blood or tissue at the site of wound creation. Other applicationswith bases having coatings include sticks that can be used in surgery tocauterize wounds during the surgical process simply by inserting thestick into the wound and contacting it with the surface of the wound.Coatings could also be used on dermal rollers, needles, and othersurgical instruments where the ability to cauterize a wound on contactis desired.

In another embodiment, the substrate or base is in the form of asemi-solid or solid composition or mixture of ingredients in which thealkali metal is dispersed, dissolved, or carried. For example, a base inthe form of a semi-solid composition comprising ingredients inconventional antiperspirants or deodorants that are applied to theaxilla is contemplated, where the alkali metal is admixed with theingredients forming the semi-solid composition. A base may also be inthe form of a paste or a thixotropic paste that is applied to a surface.Many make-ups in the cosmetic industry are pastes or thixotropic pastes,and ingredients for forming such compositions are known. Additional ofalkali metal to the pastes is contemplated, for example, by addition ofa powdered alkali metal. The paste can then be smeared onto the surface.

Because the alkali metal in the heat generating component may react withthe oxygen in air, the base and/or heat generating component may containvarious features or structures designed to prevent contact between thealkali metal until the time for its use. For example, where the base isa knife, the knife may be placed in a container with an airtight lid orpeelable covering with an inert gas, such as nitrogen or argon,contained therein. When the knife is needed, the knife may then beremoved from the container and used before the reaction between thealkali metal and oxygen progresses sufficiently to impact theeffectiveness of the knife to generate heat in situ in response to waterat the point of contact upon use. Those of ordinary skill will readilybe able to develop various protective structures and systems designed tominimize or prevent contact between the alkali metal and oxygen ormoisture in the air using the principles disclosed herein.

A. Exemplary Devices

Devices comprising a heat-generating component comprised of a substrateand an alkali metal, as detailed above, are described with reference tothe drawings and the examples. In a first embodiment, a device forcauterizing wounds is contemplated, where the device comprises a base(or substrate) having an alkali metal, such as potassium metal, sodiummetal, or NaK, deposited on the base, coupled to the base, incorporatedinto the base, and/or associated with the base. FIG. 1A illustrates adevice for cauterizing wounds, where the device is in the form of abandage 2 comprising a that supports an amount of an alkali metal, inthis example sodium free metal 6, formed into a sheet or layer andcoupled to the substrate. The embodiment in FIG. 1A illustrates thesoftness and ductility of the alkali metal and how it can be shaped tocorrespond with various desired shapes in devices, such as in theillustrated bandage.

A study was conducted to illustrate use of the device in wound closurefor improved or accelerated wound healing. With reference to Example 1,sodium metal 6 was coupled to substrate 4 using petroleum jelly to forma heat-generating component. The device was bought into contact a woundon skin. As a control, a portion of the device was contacted with aportion of the skin with no wound, i.e., uninjured, intact skin. FIG. 1Bshows the device applied over the skin 10. The device was placed on thewound and on the intact, uninjured skin for 15 seconds, whereupon it wasremoved and the effect of the heat generated by the exothermic reactionbetween the sodium metal and water at the contact site was observed. Themacroscopic appearance by unaided visual inspection and the micrographicappearance of both the uninjured skin tissue and the wounded tissue wereobserved. Photographs from the micrographic inspection are shown inFIGS. 1C-1J.

Referring to FIG. 1C, a close-up photograph of the skin surface having awounded portion 12 and the uninjured portion 14 is shown. Woundedportion 12 comprises a first wound 12 a and a second wound 12 b, eachmade with a scalpel. By visual inspection, it is apparent that no damageto the uninjured portion of the skin occurred as a result of theapplication of the device to the skin and its subsequent generation ofheat in situ. It is also apparent that the injured portion of the skin12 was cauterized as a result of the heat generated in situ by theexothermic reaction between the sodium metal in the heat-generatingcomponent of the device and water present at the site of contact on theskin. Referring to FIG. 1D, the injured area of the skin 12 was removedafter treatment with the device and a portion of the uninjured portionof the skin 14 was also removed after treatment for further inspection.Referring to FIG. 1E, a magnified view of both portions of the skin 12,14 is shown. In this view, superficial blood vessels, such as thatidentified as 16, in the injured portion of the skin 12 were notaffected by the heat generated upon application of the device and itssodium metal heat-generating component to the surface of the skin.Accordingly, the effect of the heat resulting from the exothermicreaction of the sodium metal in the device and water at the site ofcontact appears visually to be purely superficial on the outer layer ofthe wounded skin 12. The skin wound was closed or cauterized byapplication of the device, to aid and/or initiate the wound healingprocess.

Cross sectional views of the injured region of the skin and theuninjured (control) region of the skin were taken. Referring to FIG. 1F,a photomicrograph of a cross section of a wound in the injured portionof the skin 12 is shown. As seen, incision 18 extends through thestratum corneum 20 and the upper layers of the skin. The skin adjacentthe incision 18, e.g. the stratum corneum identified as the numericalidentifier 20 in the photograph, was unaffected by the heat generated insitu upon application of the device to the wounded region. Skin withinthe incision 18 reveals that a layer 22 approximately two cells deep hasbeen cauterized. This result was not expected, as it indicates that thesodium metal reacted quickly with water in the exposed tissues, and thatthe reaction stopped once the water had been consumed. This result is incontrast with conventional methods of cauterization which damage skintissues much more deeply. With reference now to FIG. 1H, aphotomicrograph further down incision 18 is shown. The dermis of theskin shows that a cauterized layer 24 is still very thin relative to thesurrounding tissue, which was also unexpected. FIG. 1G shows a secondincision 26 of wound 12 (different from the incision shown in FIG. 1F).The photomicrograph confirms the results observed with respect to theincision 18 of FIG. 1F—that the outer surface 28 of the skin, includingthe stratum corneum, was unaffected by the heat generated uponapplication of the device and its heat generating component comprisingsodium metal, and that a layer 30 approximately two cells deep wassealed or cauterized as a result of the heat released by the exothermicreaction between water in the wounded tissue and the sodium metal in theheat-generating component.

Referring to FIG. 1I, a photomicrograph of a cross section of theuninjured skin region 14 is shown. By inspection, it is apparent thatthe appearance of the uninjured skin is entirely normal through all ofthe layers of the skin. This result indicates that the uninjured skin,not having much if any water available for reaction with the sodiummetal in the heat-generating component of the device when it was appliedto the uninjured skin site, did not generate heat by an in situ reactionwith the sodium metal during the time the bandage-like device wasapplied to the skin surface. FIG. 1J, which is a photomicrograph ofanother cross section of the uninjured skin 14, confirms the resultobserved in FIG. 1I, that the layers of the uninjured skin wereunaffected by contact with the device, and that a lack of water at thesite of contact limited the exothermic reaction with the sodium metal inthe device.

From the study described in Example 1 and the drawings in FIGS. 1A-1J,it can be appreciated that upon application of the device to a surface,the amount of heat generated is controlled by, limited by, orproportional to the amount of alkali metal and/or the amount of water atthe surface that is available for reaction with the alkali metal.

Another embodiment of a device and use thereof is detailed in Example 2.In this embodiment, a device designed to render a surface substantiallyaseptic is contemplated. As a model for a surface to be treated, petridishes filled with lysogeny broth were streaked with Escherichia coli(E. coli). One of the petri dishes was designated to be a control orreference, and was not further treated during the study. A second petridish was treated with water. A third petri dish was treated with a waterand sodium metal for about 10 seconds. Photographs of the petri disheswere taken a time points of 0 hours (i.e., at the time of treatment) andat 4 hours, 24 hours and 48 hours post-treatment to observe growth ofthe E. coli population. Results are shown in FIGS. 2A-2L.

Referring to FIGS. 2A-2C, the dish shown in FIG. 2A was the referencedish, the dish in FIG. 2B was actively washed with sterile water, andthe dish in FIG. 2C was contacted with sodium metal particles for lessthan 10 seconds after actively washing with sterile water. FIGS. 2A-2Cshow the appearance of the E. coli streaks as originally applied to eachdish following introduction of the water and water/sodium metal mixture(time=0 hours). The dishes 4 hours after treatment are shown in FIGS.2D-2F, where the dish in FIG. 2D was the reference dish, FIG. 2E was thewater treated dish, and FIG. 2F was the water/sodium metal treated dish.Some growth of E. coli in the reference dish (FIG. 2D) can be seen atthis time point (4 hours). The dishes 24 hours after treatment are shownin FIGS. 2G-2I, where the dish FIG. 2G was the reference dish, FIG. 2Hshows the water treated dish, and FIG. 2I shows the sodium metal/watertreated dish. Significant E. coli growth can be seen in the referenceand water treated dishes, but no bacterial growth was observable in thesodium/water treated dish. The dishes 48 hours after treatment are shownin FIGS. 2J-2L, where the dish FIG. 2J was the reference dish, FIG. 2Kshows the water treated dish, and FIG. 2L shows the sodium metal/watertreated dish. As can be observed, both the reference and water treateddishes experienced significant growth of the E. coli bacteria, while nobacterial growth was observed in the sodium metal/water treated dish.This result indicates that the heat generated in situ from theexothermic reaction between the sodium metal and the water present atthe treatment surface can be used to render the infected surfacesubstantially aseptic. Accordingly, in one embodiment, a device isprovided that is comprised of a heat-generating component having analkali metal carried on a substrate. The alkali metal is present in anamount sufficient to react exothermically with water at the site ofcontact on a surface to be treated to generate heat. The heat isgenerated in an amount sufficient to raise the temperature of the siteof contact and, in some cases depending on the thermal properties of thesurface, a peripheral zone about the site of contact. The rise intemperature at the site of contact, and optional peripheral zone, issufficient to achieve an intended effect, such as destruction of apathogen at the site or alteration of a condition of a tissue.

In another study, described in Example 3, a device for rendering asurface aseptic was evaluated. In this study, the infected surface wasmodeled by a petri dish with a plurality of E. coli bacterial colonies.The petri dish is shown in FIG. 3A. A device having a heat-generatingcomponent comprised of a substrate and sodium metal (like that describedin Example 1) was applied to a portion of the surface of the dish todefine a point of contact. No exogenous water was applied to the surfaceto be treated with the device, as bacteria retain a coating which tendsto bind water inherently thereto. FIG. 3B shows the dish followingcontact with the heat-generating component 32 of the device to thebacteria-infected surface at a point of contact. As can be observed fromthe visual appearance of the E. coli bacterial colonies after treatment(dish in FIG. 3B), heat generated in situ upon application of the deviceand its heat-generating component comprising sodium metal reacted withwater present in situ at the point of contact (i.e., water in thebacterial colonies). The heat raised the temperature at the site ofcontact to a temperature sufficient to destroy the bacteria. This studyillustrates that the devices contemplated herein that comprise aheat-generating component comprising an alkali metal generate heat insitu by an exothermic reaction with water present at the point ofcontact at the surface to be treated, and that the heat generated issufficient to raise the temperature of the treatment zone to atemperature sufficient to render it the treatment zone substantiallyaseptic. Reference to ‘treatment zone’ intends the point of contact anda zone adjacent the point of contact that is heated to a temperaturesufficient to achieve the desired effect (e.g., destroying a pathogen oraltering a state of a tissue).

In another embodiment, devices are constructed for generation of heatfor the purpose of attenuating or reducing on a temporary or permanentbasis excessive sweating. Devices constructed for this application aredescribed with reference to Examples 4-6. In a first exemplary device, aheat-generating component was modeled by a mixture of a NaK alloyadmixed with an anhydrous aluminum salt. The heat-generating componentwas applied to shaved axilla of a subject suffering from excessivesweating (Example 4). Before application of the heat-generatingcomponent, the shaved axilla were stain tested to visualize sweatproduction. In the stain test, iodine solution was applied to the shavedaxilla, the iodine-treated area was dried, and then the iodine-treated,dried area was dusted with starch. When sweat is excreted in the axillaregions, a reaction between the iodine and the starch in the presence ofthe sweat occurs and turns the iodine-treated area black in color.Photographs of the axilla before treatment with the heat-generatingcomponent are shown in FIGS. 4A-4B. FIG. 4A shows the left and rightaxilla of the male patient taken immediately after dusting with starchand the photograph in FIG. 4B shows the left and right axillar of thesame patient 5 minutes later. The presence of the black color indicatesthe severity of the hyperhidrosis present in this patient and that mostof the axilla skin is participating in creating hyperhidrosis in thispatient.

The heat generating mixture of the NaK alloy admixed with anhydrousaluminum salt was applied directly to the axilla regions for a treatmentperiod of about 10 minutes. Following application of the heat-generatingmixture to the axilla, the axilla regions were stain tested. Photographsof the regions were taken at time equal 0 minutes corresponding toimmediately prior to stain test treatment and at 5 minutes post staintest treatment and at 10 minutes post stain test treatment, while theheat-generating mixture was still present in the axilla regions. Thephotographs are shown in FIGS. 4C-4E.

The photograph in FIG. 4C shows the left and right axilla followingtreatment by applying liquid NaK in an anhydrous aluminum salt basedirectly to the skin for a treatment period (10 minutes). The photographin FIG. 4C was taken at time equal 0 minutes immediately prior to staintest treatment. The photograph in FIG. 4D shows the axilla of thepatient at 5 minutes post stain test treatment while the NaK solution isstill applied, and FIG. 4E shows the axilla of the patient at time equal10 minutes post stain test treatment at the conclusion of the NaKapplication period. When compared with the baseline data in FIG. 4Bmarked improvement is observed after a single treatment of theheat-generating component. That is, a marked reduction in sweatproduction occurred. During the treatment period, the NaK alloy enteredthe sweat ducts and/or the sweat glands and reacted with water presentin the ducts and/or glands as it was being produced (released) by thepatient. The alloy and water in the sweat react in situ in an exothermicreaction to generate heat. Without being bound by any theory, it appearsthat the heat generated by the reaction raises the temperature at thetreatment site to a temperature sufficient to ablate the ducts and/orglands, causing their destruction and preventing them from operating toproduce the excess amounts of sweat consistent with hyperhidrosis.Because of the ablation of the sweat ducts and/or glands, a permanentreduction of the axillary skin's ability to excrete sweat may beachieved, as the ablation may be permanent, as the skin tissue may notregenerate the ablated ducts and/or sweat glands.

In another study, a composition of an alkali metal admixed with otheringredients suitable for forming a skin-safe heat-generating compositionfor application to the skin was prepared. The purpose of this study wasto illustrate that the alkali metal, e.g., sodium metal, potassiummetal, or sodium and potassium metal alloy, may be incorporated withother ingredients to form a final composition for application to asubject. These additional ingredients may be actives or inactivesselected to perform a variety of compositional or therapeutic effects.In this study, a composition comprised of NaK and pure mineral oil wasprepared, where the ratio of the components was 1 part of NaK to 20parts of mineral oil (1:20) by volume. As described in Example 5, thecomposition was applied to the left axilla of a patient diagnosed withhyperhidrosis and allowed to remain for 5 minutes before being removed.The left axilla was stain tested to visualize sweat production, andphotographs of the left axilla of the patient were taken at thefollowing time points: after stain testing for 90 seconds prior totreatment with the NaK/mineral oil solution (FIG. 5A), followingtreatment with the NaK/mineral oil solution after stain testing for 90seconds (FIG. 5B). Treatment with the NaK/oil mixture was repeated for 5minutes and the area when then stain tested. A photograph of the regionwas taken 90 seconds after stain testing (FIG. 5C).

FIG. 5A shows the left axilla of the patient after stain testing for 90seconds prior to treatment with the NaK/mineral oil solution. FIG. 5Bshows the left axilla of the same patient following treatment with theNaK/mineral oil solution as previously described after stain testing for90 seconds. FIG. 5B indicates marked improvement over the baselinetesting shown in FIG. 5A. To see if additional improvement could beobtained, the treatment with the NaK/mineral oil solution was againrepeated for 5 minutes and stain testing for 90 seconds was undertaken.FIG. 5C is a photomicrograph of the twice-treated area 90 seconds afterstain testing. Additional marked improvement is noted, as evidenced by afurther reduction in sweat production (reduction in black color producedin the treatment region). At a glandular level, of the effect of theheat generated in situ and concomitant temperature increase may betemporary or permanent depending on the extent of ablation of thetissues.

A wide variety of alkali metal/mineral oil ratios may be employed invarious implementations, including about 1:1 to about 1:1000. Otheractive and inactive ingredients that could be employed with alkalimetal/mineral oil compositions include any anhydrous base materialsincluding anhydrous synthetic polymers and mixtures of anhydrous basematerials and anhydrous synthetic polymers.

In other embodiments, the alkali metal may be mixed with an aluminumsalt, magnesium salt, or a combination of both. An example of thisembodiment is detailed in another study described in Example 6. In thisstudy, a device with a heat-generating component in the form of amixture of NaK and an aluminum salt-containing base was prepared. Theheat-generating component was in the form of semi-solid, like anantiperspirant semi-solid. The heat-generating component contained 1part of NaK to 100 parts of antiperspirant containing the aluminum salt(1:100) by volume. The heat-generating component was applied topicallyto the right axilla of a patient diagnosed with hyperhidrosis andallowed to stand for 5 minutes prior to being removed. The right axillawas then stain tested as set forth in Example 4. Photographs of theright axilla prior to treatment with the NaK/antiperspirant compositionafter 90 seconds have elapsed during a stain test (FIG. 6A) andfollowing treatment with the NaK/antiperspirant composition after 90seconds had elapsed during a stain test (FIG. 6B) were taken.

FIG. 6A shows the right axilla prior to treatment with theNaK/antiperspirant composition and 90 seconds after a stain test. FIG.6B shows the right axilla following treatment with theNaK/antiperspirant composition and 90 seconds after a stain test. Thisstudy indicates that a substantial reduction in sweat product isachieved after a single treatment of the heat-generating device, andthat two, three, four, five, or more treatments may be used to achievefurther reduction in sweat production via ablation of the sweat ductsand/or sweat glands or other structures in the skin being treated.

Alkali metal/antiperspirant compositions may include any of a widevariety of ratios of alkali metal to aluminum salt-containingcompositions. Example of such ratios include about 100:1 to about1:1000. Other active and inactive ingredients that could be employedwith alkali metal compositions include anhydrous polymers or mixtures ofanhydrous polymers, and some examples of suitable ingredients areitemized in the table of Example 6. Those of ordinary skill will readilybe able to select various active and inactive ingredients using theprinciples disclosed herein.

Contemplated is a kit that comprises a device as described herein incombination with instructions for use, and, optionally, a wipecomprising a solvent for cleansing the site of contact to which thedevice is intended to be applied. In one embodiment, the wipe is a gauzepad and in one embodiment the solvent is isopropyl alcohol.

II. METHODS OF USE

The heat-generating devices described herein can be used for a varietyof purposes, and several are now described.

A. Rendering a Surface Substantially Aseptic

In a first aspect, a method for rendering surfaces substantially asepticis contemplated. The surfaces intended for use in this method encompassany surface on which a pathogen or undesirable species resides or grows,including skin surfaces, counter top or bench top surfaces, or surgicalinstrument surfaces. With respect to skin surfaces, the topical skintreatment of pathogens on the skin or that involve moisture secretion bythe skin include, by way of non-limiting example, acne, fungalinfections, removal of warts (applied before or after removal of thewart), cold sores (Herpes simplex), and any other pathogen that can bekilled or denatured through application of heat.

Various device implementations that contain sodium metal and/or NaK maybe developed for use to create or render a surface substantiallyaseptic. In these implementations, the device comprises aheat-generating component as described above and an applicator that isshaped/designed so that a user can contact the heat-generating componentwith the surface in such a manner to render it substantially aseptic.For example, where the surface to be rendered aseptic is skin, the usermay first apply an amount of water to the skin to moisten it or hydratethe area to be treated. In most cases, addition of exogenous water tothe treatment size is not required. Holding the applicator, the userbrings the heat-generating of the device into contact with the skin atthe site to be treated, thereby generating heat during reaction of thesodium metal with the water on the skin. In one embodiment, the deviceis held stationary at the treatment site, until an indicator light onthe device indicates that the temperature at the point of contact hasdecreased to a preselected temperature, or has decreased from itsmeasured maximum temperature during treatment by a certain percentage.In various implementations, such as in the holder implementations, thealkali metal is included in the applicator in a retractable fashion. Inother embodiments, the alkali metal of the heat generating component ison an outer surface of the applicator.

In other embodiments, the base or substrate is a container that holds aquantity of dry alkali metal therein and which is designed to allow theuser to contact their hands with the powdered alkali metal. In suchimplementations, the container could be, by non-limiting example, apouch, a dish, a box, a bag, a reclosable bag, or any other structurecapable of holding dry alkali metal and providing access to a user. Asthe user contacts the powdered alkali metal with their skin, the dryalkali metal and in situ water undergo an exothermic reaction togenerate heat. The heat is generated in an amount that will, forexample, cauterize any wound on the user's hand. Also, the exothermicreaction may create, in addition to heat, an alkali metal hydroxide,such as sodium hydroxide or potassium hydroxide. The heat and/or alkalihydroxide kills and/or denatures pathogens on the surface to be treated(e.g., in this embodiment, a user's hands). Thus, in some embodiments,the device can simultaneously cauterize and render a surfacesubstantially aseptic.

The applicator may be a needle, wipe or sponge. In these embodiments,the device can render an area within a patient or other area withinanother structure aseptic. It may also aid in performing injectionlipolysis through the alkali metal reacting with water in situ, e.g.,water stored in fat tissue adjacent to the location where the needle isinserted. In such implementations, the needle may be hypodermic andhollow. In other implementations, the needle may not be hollow and thealkali metal is present as a coating on the needle.

In other embodiments, the device is intended for use in sterilizinginstruments. In this embodiment, the base or substrate can be astructure designed to hold one or more instruments for sterilization andthe alkali metal is present at a suitable location. Instruments placedinto the base are sterilized when the alkali metal undergoes itsexothermic reaction with water present on the instruments, and thereaction generates an amount of heat sufficient to sterilize the surfaceof the instruments. In other embodiments, the device is designed tocontact the alkali metal with a surface of an instrument to render itssurface sterile, where the instrument may be pre-wetted with water ormay have residual water present from rinsing after use.

In the methods of use described herein, various approaches andstructures may be used to prevent or minimize contact between theambient air and the alkali metal before the device is ready to be used.Such approaches and structures gas impermeable packaging, nitrogen orother inert gas purging systems that keep oxygen from contact with theheat-generating component of the device while not in operation.

B. Wound Closure

In another embodiment, devices described herein are used for closure ofa wound, by cauterizing the wound as a result of the temperatureincrease at a site of contact, and a surrounding peripheral area to forma treatment zone, by heat generated by the exothermic reaction betweenthe alkali metal of the device and water present at the site of contact.Cauterization of a wound closes the wound, to aid in and/or acceleratethe wound healing process. Cauterization may be employed in varioussituations where wounds are formed, such as surgical procedures, wartremoval, cryogenic therapies, battle wounds, extreme sports injuries inremote locations, and many other situations where the water from theblood and tissue in the wounds can be reacted with the alkali metal tocauterize the wound.

As discussed above, heat and the concomitant temperature increaseachieved during use of the device is also sufficient to render a surfaceat the point of contact (and surrounding treatment zone) aseptic.Accordingly, a method of simultaneously cauterizing a wound for healingand rendering a surface substantially aseptic is contemplated. Forexample, in a laboratory situation where pathogens are being handled andwhere the researcher wishes to ensure the skin surface of the hands isintact, the researcher may lightly moisten her hands and then applypowdered sodium metal or NaK, permitting any open wounds on the hands tobe closed and her hands to be rendered aseptic. After handing thepathogens, the researcher may repeat the process, and ensure that herhands are substantially free from the pathogens. Other situationsinvolve battlefield injuries where wounds need to be stabilized beforetreatment in a hospital or in a battlefield hospital where a surgeondoes not have access to any or a reliable source of electricity topermit other hand or wound sterilization systems to be employed. A widevariety of potential use situations and structures are possible usingthe principles disclosed herein. In medical applications, the ability tocauterize and/or render a surface aseptic on contact may be useful orcritical depending upon the conditions. For example, on a battlefield,there may be no electricity or water present, and the need to stopbleeding and stop infection while waiting to get an injured soldier tomedical attention may be critical.

C. Excessive Sweating: Hyperhidrosis and Perceived Excessive Sweating

Hyperhidrosis is a medical condition characterized by excessive sweatingin the armpits (axillae), palms, soles of the feet, face, scalp, and/ortorso. Hyperhidrosis when not secondary to a known underlying medicalcondition is referred to as primary focal hyperhidrosis. Primary focalhyperhidrosis is defined as excessive, bilateral, and relativelysymmetric sweating occurring in at least one of the following sites: theaxillae, palms, soles, or craniofacial region (Hornberger, J. et al., J.Am. Acad. Dermatol., 51:274-86 (2004)). Criteria recommended forestablishing the diagnosis of primary focal hyperhidrosis include (1)focal, visible, excessive sweating of at least 6 months duration withoutapparent cause with at least two of the following characteristics: (i)bilateral and relatively symmetric; (ii) impairs daily activities, (iii)frequency of at least one episode per week; (iii) age of onset less than25 years; (iv) positive family history; and (v) cessation of focalsweating during sleep (Id). In subjects that report excessive sweatingyet a medical diagnosis of primary focal hyperhidrosis is not satisfied,these subjects have a perceived excessive sweating. The methods oftreatment described herein for treating or reducing excessive sweatingencompass hyperhidrosis as a medical condition, primary focalhyperhidrosis and secondary hyperhidrosis, as well as perceivedexcessive sweating.

In this aspect, a method for treating excessive sweating, by reducingtemporarily or permanently the amount of sweat produced in each episodeof sweating, is provided. The method comprises contacting the skin ofthe subject at a site of contact where excessive sweating occurs (e.g.,axillae, palms, craniofacial region) with a device as described herein.The alkali metal in the heat generating component of the device reactswith water in the sweat at the site of contact to generate heat in situ,where the heat is generated in an amount controlled by or proportionalto the amount of water present at the site of contact and where the heatis generated in an amount sufficient to raise the temperature of thepoint of contact (and preferably a zone around the point of contact) toa temperature that ablates the sweat ducts and/or sweat glands to renderthem less able to produce sweat.

In one embodiment, a reduction in sweat production is observed for aperiod of at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1week, 2 weeks, 3 weeks or 1 month. The method comprises, in otherembodiments, repeating the step of contacting the skin with a device toachieve a further reduction in sweat production or a subsequentreduction in sweat production for a subsequent period of time. Thereduction in sweat production is ascertained subjectively, in oneembodiment, via a series of questions to the subject, such as those inthe classification scales described below (HDDS and HHIQ). In anotherembodiment, the reduction in sweat production is ascertainedobjectively, such as gravimetrically or via an iodine test. Ingravimetric measurements, a piece of filter paper is weighed and is thenapplied to the palm or axilla (or other body region) for a period oftime measured with a stopwatch. The paper is then weighted and the rateof sweat production is calculated in mg/min. In one embodiment, themethod is effective to achieve at least a 25% reduction in sweatproduction, more preferably at least a 50% reduction in sweatproduction, for a period of 3 days, 5 days or 1 week.

In one embodiment, the method is used for reduction of excessivesweating in a patient experiencing moderate to severe excessivesweating. Classification of hyperhidrosis as mild, moderate or severeis, in one embodiment, made using the Hyperhidrosis Disease SeverityScale (HDDS). The HDDS is a four-point scale designed to assess theseverity of hyperhidrosis in clinical practice and to assess theeffectiveness of hyperhidrosis treatment. The scale can be administeredby a clinician or by the patient, and asks the patient to choose fromthe following four statements the one that best applies:

-   -   1. My sweating is never noticeable and never interferes with my        daily activities.    -   2. My sweating is tolerable but sometimes interferes with my        daily activities.    -   3. My sweating is barely tolerable and frequently interferes        with my daily activities.    -   4. My sweating is intolerable and always interferes with my        daily activities.        Selection of 3 or 4 indicates severe hyperhidrosis and selection        of 2 indicates moderate hyperhidrosis, and a selection of 1        indicates mild hyperhidrosis. Other measures of hyperhidrosis        include the Hyperhidrosis Impact Questionnaire® (HHIQ),        gravimetric sweat production, and dermatology quality of life        index (DLQI). The validity and reliability of the HHIQ scale,        and its utility in measuring the burden of the disease and its        effect in patients, is documented in the literature, for        example, by Teale et al., Qual Life Res., 11:702 (2002); Naumann        et al., Br. J Dermatol, 147:1218 (2002); and Strutton et al., J.        Am Acad Dermatol, 51:241 (2004).        D. Treatment of Symptoms Associated with Allergies

In another embodiment, a method for ameliorating or treating symptomsassociated with allergies is provided. A common symptom of allergies,especially seasonal allergies, is a runny nose. Use of the devicedescribed herein to reduce or substantially reduce nasal discharge orother symptoms of seasonal allergies is contemplated, by contacting thedevice to a location on a patient with excessive water-related swellingor discharge. Upon contact, the alkali metal in the heat generatingcomponent of the device reacts with water in the discharge at the siteof contact to generate heat in situ, where the heat is generated in anamount controlled by or proportional to the amount of water present atthe site of contact and where the heat is generated in an amountsufficient to raise the temperature of the point of contact (andpreferably a zone around the point of contact) to a temperature thatablates the tissue region, rendering it less able to produce discharge.In one embodiment, the method is used to treat symptoms of sinusitis,where the sinusitis is associated with either an infectious or aninflammatory standpoint, thus allowing the symptoms and signs ofsinusitis to be alleviated. Any of the various devices disclosed hereincan be used in this method, including pastes and nasal swabs to applythe alkali metal to the treatment site.

E. Ablation of Tissue

In another embodiment, a method for ablating tissue with the devicesdescribed herein is contemplated. For example, the devices may be usedto reduce or substantially reduce the tumor mass of a cancer or enlargedorgan following at least one application of the device to the affectedlocation. Any of the various devices disclosed herein may be used. Inparticular implementations, infusion catheters, needles, and cannulasmay be utilized to transport the heat-generating component to thetreatment site.

The devices may also be used to reduce or substantially reduce adiposetissue volume following at least one application of the heat-generatingcomponent to a location on a patient containing an undesirable amount ofor shape of fat tissue. Any of the various devices disclosed herein maybe used. In particular implementations, infusion catheters, needles, andcannulas may be utilized to transport the heat-generating component tothe treatment site. Particular areas which may be treated includesubmental fat, breast tissue (to aid in breast lifting/reducing),thighs, buttocks, hips, cheeks, the neck, and other areas which containadipose tissue and/or fat to be reduced/altered.

III. EXAMPLES

The following examples are illustrative in nature and are in no wayintended to be limiting.

Example 1 Device in the Form of a Bandage for Wound Closure

A device was prepared using a sterile gauze pad as a substrate. Sodiummetal was mixed into petroleum jelly to form a paste, which was thenapplied to one side of the substrate. The opposing side of the substratewas overlayed with a backing member having a peripheral adhesive to forma bandage-like device (see FIG. 1A).

A section of viable porcine skin was obtained, and a wound was madeusing a scalpel. The device was applied to the porcine skin so that thesubstrate with sodium meal was in contact with the wound and withadjacent uninjured, intact skin, the latter site of contact serving as acontrol. The device was left in place for 15 seconds and removed. Theappearance and micrographic appearance of both the uninjured skin tissueand the wounded tissue was observed. Results are shown in FIGS. 1C-1J.

Example 2 Streak Testing with Escherichia coli

Three petri dishes containing lysogeny broth (LB) were prepared andstreaked with a culture of JM109 competent Escherichia coli obtainedfrom Sigma-Aldrich of St. Louis, Mo. One petri dish was designated asthe reference dish and was untreated. The second dish was activelywashed with sterile water after streaking with E. coli, and the thirddish was contacted with sodium metal particles for less than 10 secondsafter actively washing with sterile water. Photographs of the disheswere taken to observe the appearance of the E. coli bacterial streaks asoriginally applied to each dish following introduction of the water andwater/sodium metal mixture (time=0 hours, FIGS. 2A-2C) and afterincubation under standard growth conditions, at a temperature of 37° C.,for 48 hours. The dishes were photographed at 4 hours, 24 hours and at48 hours, and the results are shown in FIGS. 2D-2F, FIGS. 2G-2I, andFIGS. 2J-2L, respectively.

Example 3 Aseptic Capability of Sodium Metal Through Direct Contacting

A petri dish containing LB broth was cultivated with an E. colibacterial population to create a plurality of colonies distributedacross the surface of the dish. After the bacterial colonies wereestablished, a device like that described in Example 1 was applied tothe surface of the LB broth and E. coli colonies. No additional(exogenous) water was added. The dish was photographed before (FIG. 3A)and after (FIG. 3B) treatment to observe the effect of the heatgenerated in situ on the bacterial populations.

Example 4 Device for Generation of Heat In Situ

A male patient diagnosed with hyperhidrosis was prepared for treatmentwith a device by shaving the hair from both axilla. The shaved area wasstain tested using an iodine-starch indicator test. Iodine solution wasapplied to the shaved axilla, the iodine-treated area was dried, andthen the iodine-treated, dried area was dusted with starch. A photographof the axilla of the male patient taken immediately after dusting withstarch and at 5 minutes later are shown in FIGS. 4A-4B.

An alkali metal in the form of an alloy of Na and K (hereafter NaK)admixed with an anhydrous aluminum salt was prepared. The mixture wasapplied directly to the axilla regions for a treatment period of about10 minutes. Following application of the heat-generating mixture to theaxilla, the axilla regions were stain tested, as described in thepreceding paragraph. Photographs of the regions were taken at time equal0 minutes corresponding to immediately prior to stain test treatment andat 5 minutes post stain test treatment and at 10 minutes post stain testtreatment, while the heat-generating mixture was still present in theaxilla regions. The photographs are shown in FIGS. 4C-4E.

Example 5 Antiperspirant Solution for Generation of Heat In Situ

A composition of NaK and pure mineral oil was prepared at a ratio of 1part of NaK to 20 parts of mineral oil (1:20) by volume. The resultingmixture was a silvery grey color following sonication for 30 seconds.The composition was then applied to the left axilla of a patientdiagnosed with hyperhidrosis and allowed to remain for 5 minutes beforebeing removed. The left axilla was then treated using iodine and starchfor stain testing, as described in Example 4. Photographs of the leftaxilla of the patient were taken: after stain testing for 90 secondsprior to treatment with the NaK/mineral oil solution (FIG. 5A),following treatment with the NaK/mineral oil solution after staintesting for 90 seconds (FIG. 5B). Treatment with the NaK/oil mixture wasrepeated for 5 minutes and the area when then stain tested. A photographof the region was taken 90 seconds after stain testing (FIG. 5C).

Example 6 Antiperspirant Device for Generation of Heat In Situ

A mixture of NaK and an aluminum salt-containing composition in the formof a clinical strength antiperspirant formulation marketed under thetradename DEGREE CLINICAL PROTECTION® by Conopco Inc. (Unilever) ofLondon, UK was prepared. The particular components of the antiperspirantformulation are set forth in the table below. The mixture contained 1part of NaK to 100 parts of antiperspirant containing the aluminum salt(1:100) by volume. The resulting mixture was a whitish solid paste.

The NaK/antiperspirant composition was applied topically to the rightaxilla of a patient diagnosed with hyperhidrosis and allowed to standfor 5 minutes prior to being removed. The right axilla was then staintested as set forth in Example 4. Photographs of the right axilla priorto treatment with the NaK/antiperspirant composition after 90 secondshave elapsed during a stain test (FIG. 6A) and following treatment withthe NaK/antiperspirant composition after 90 seconds had elapsed during astain test (FIG. 6B) were taken.

Ingredient aluminum zirconium 20 g in 100 g (20%) tetrachlorohydrex GLY(aluminum cation) NaK 1 g in 100 g cyclopentasiloxane (inactive)dimethocone (inactive) microcrystalline wax (inactive) C18-C36 acidtriglyceride (inactive) fragrance (inactive) silica (inactive) zea mays(corn starch) (inactive) dimethicone crosspolymer (inactive) butylatedhydroxytoluene (BHT) (inactive)

Example 7 Diagnostic Tool for Hyperhidrosis and Treatment Thereof

A female subject concerned with sweating in her axilla and facial areais asked by her clinician to complete the Hyperhidrosis Disease SeverityScale (HDDS), which asks the subject “How would you rate the severity ofyour hyperhidrosis?” 1. My sweating is never noticeable and neverinterferes with my daily activities. 2. My sweating is tolerable butsometimes interferes with my daily activities. 3. My sweating is barelytolerable and frequently interferes with my daily activities. 4. Mysweating is intolerable and always interferes with my daily activities.The subject is asked to select the statement from choices 1, 2, 3 and 4that best reflects her experience with sweating of her axilla and face.The subject chooses statement 3, and is assigned a diagnosis of severehyperhidrosis. The subject is prescribed a device in the form of anantiperspirant stick comprising a sodium-potassium alloy according toExample 6 and applies the composition to her axilla and forehead onceper week.

Additional Embodiments of the disclosed device are now recited.

Implementations of devices for cauterizing wounds may include a base andone of sodium metal or a sodium and potassium metal alloy coupled withthe base where the base is configured to allow a user to apply the oneof the sodium metal or the sodium and potassium metal alloy to an openwound of a patient to cauterize the open wound.

Implementations of devices for cauterizing wounds may include one, all,or any of the following:

The base may be designed to prevent contact of the one of sodium metalor the sodium and potassium metal alloy with one of oxygen or wateruntil just prior to use by a user.

The one of sodium metal or the sodium and potassium metal alloy may beincluded within a portion of the base.

The base may be a bandage and the one of sodium metal or the sodium andpotassium metal alloy may be one of included within and included on asterile dressing coupled to the bandage.

The one of sodium metal or the sodium and potassium metal alloy may becoupled with the base through being coated on a portion of a surface ofthe base.

The base may be selected from the group consisting of a dermal roller, aknife, a surgical instrument, a stick, a dermal pen, and a needle.

Implementations of a device for rendering a surface substantiallyaseptic may include an application and one of sodium metal or a sodiumand potassium metal alloy coupled with the applicator where theapplicator is configured to allow a user to apply the one of sodiummetal or the sodium and potassium metal alloy to the surface to renderthe surface substantially aseptic.

Implementations of the device may contain one, all, or any of thefollowing:

The applicator may be configured to prevent contact of the one of sodiummetal or the sodium and potassium metal alloy with one of oxygen orwater until just prior to use by a user.

The one of sodium metal or the sodium and potassium metal alloy may beincluded within the applicator.

The applicator may be a container adapted to enable the contacting ofsodium metal in powdered form with a user's hands to render the user'shands substantially aseptic, cauterize one or more wounds on the user'shands, and/or both render the user's hands substantially aseptic andcauterize one or more wounds on the user's hands.

The applicator may be a needle, a wipe, or a sponge.

The applicator may be a sterilizer which may be configured to mix waterwith the one of sodium metal or the sodium and potassium metal alloy togenerate heat sufficient to render a surface of an item being sterilizedsterile.

The applicator may be a sterilizer which may be configured to contactthe one of sodium metal or the sodium and potassium metal alloy with asurface of an item to render the surface sterile.

Implementations of a device for rendering a wound substantially asepticand for cauterizing the wound may include a wound contacting device andone of sodium metal and a sodium and potassium metal alloy coupled withthe wound contacting device. The wound contacting device may beconfigured to allow a user to apply the one of sodium metal and thesodium and potassium metal alloy to the wound to render the woundsubstantially aseptic and simultaneously cauterize the wound.

Implementations of the device may include one, all, or any of thefollowing:

No external or exogenous water may be used by the wound contactingdevice.

The wound contacting device may be a bandage including a dressingcoupled with the one of sodium metal and the sodium and potassium metalalloy.

The bandage may be configured to, after rendering the woundsubstantially aseptic and simultaneously cauterizing the wound, ensurethat all of the one of sodium metal and the sodium and potassium metalalloy are consumed.

The bandage may be configured to render the wound substantially asepticand simultaneously cauterize the wound after a passage of apredetermined period of time.

Implementations of a composition for treating hyperhidrosis may includeone of sodium metal or a sodium and potassium metal alloy where the oneof sodium metal or the sodium and potassium metal alloy is configured topermit a user to apply the one of sodium metal or the sodium andpotassium metal alloy to a location of a patient's skin and ablate oneof at least one sweat gland or at least one sweat duct in that location.

Implementations of the composition may include one, all, or any of thefollowing:

The composition may include mineral oil.

The mineral oil may be mixed with the sodium and potassium metal alloyin a ratio of 1:20 parts of sodium and potassium metal alloy to parts ofmineral oil by volume.

The composition may include a salt-containing composition.

The salt-containing composition may further include aluminum, magnesium,or any combination thereof.

The salt-containing composition may include aluminum and may be mixedwith the sodium and potassium metal alloy in a ratio of 1:100 parts ofsodium and potassium metal alloy to parts of aluminum salt-containingcomposition by volume.

The composition may be further configured to substantially reducehyperhidrosis following two or more applications of the composition to alocation on a patient containing at least one sweat gland throughablation of the at least one sweat gland.

The composition may be further configured to substantially reducehyperhidrosis following a single application of the composition to alocation on a patient containing at least one sweat gland throughablation of the at least one sweat gland.

The composition may further include an anhydrous polymer. In oneembodiment, all components or ingredients of the composition and thedevice are anhydrous.

Implementations of sodium compositions may include sodium metal or asodium and potassium metal alloy where the sodium metal or sodium andpotassium metal alloy is coupled to an applicator or a base configuredto permit a user to apply the sodium metal or the sodium and potassiummetal alloy to: a location in a patient's nose to ablate tissue toreduce nasal discharge, improve airflow, reduce pain symptoms, reduceseasonal allergy symptoms, or any combination thereof; an enlargedgland; adipose tissue containing fat in need of reduction in volume orchange in shape; or a cancer lesion or cancer tumor.

Implementations of sodium compositions may include one, all, or any ofthe following:

The enlarged gland may be selected from the group consisting of prostategland, pilosebaceous unit, or a sebaceous gland.

This disclosure, its aspects and implementations, are not limited to thespecific components, assembly procedures or method elements disclosedherein. Many additional components, assembly procedures and/or methodelements known in the art consistent with the intended heat generatingsystems will become apparent for use with particular implementationsfrom this disclosure. Accordingly, for example, although particularimplementations are disclosed, such implementations and implementingcomponents may comprise any shape, size, style, type, model, version,measurement, concentration, material, quantity, method element, step,and/or the like as is known in the art for such heat generating systems,and implementing components and methods, consistent with the intendedoperation and methods.

In places where the description above refers to particularimplementations of heat generating systems and implementing components,sub-components, methods and sub-methods, it should be readily apparentthat a number of modifications may be made without departing from thespirit thereof and that these implementations, implementing components,sub-components, methods and sub-methods may be applied to other heatgenerating systems.

What is claimed is:
 1. A device, comprising: a substrate having a firstsurface and a second surface, and an alkali metal embedded in orintegral with the substrate, wherein the alkali metal is a neat alkalimetal selected from sodium and potassium, and wherein the neat alkalimetal is present in an amount sufficient to generate an amount of heatin situ when the substrate contacts a treatment surface separate fromthe device to bring the neat alkali metal in contact with water presentat the treatment surface, wherein the amount of heat generated islimited by an amount of or moles of water at the treatment surface. 2.The device of claim 1, wherein the first surface of the substrate is afirst planar surface and the second surface of the substrate is anopposing planar surface.
 3. The device of claim 2, wherein the firstplanar surface is a contact surface or distal surface for contact withthe treatment surface.
 4. The device of claim 2, wherein the opposingplanar surface is a proximal surface in which the alkali metal is incontact.
 5. The device of claim 1, wherein the alkali metal additionallyforms a layer on the first surface of the substrate.
 6. The device ofclaim 5, wherein the layer forms a discontinuous layer on the firstsurface of the substrate.
 7. The device of claim 5, wherein the alkalimetal additionally forms a discontinuous layer on the second surface ofthe substrate.
 8. The device of claim 1, wherein the substrate is a meshhaving open regions and the alkali metal is embedded in a portion of theopen regions.
 9. The device of claim 1, wherein the amount of heatgenerated is limited by the amount of or moles of alkali metal selectedfrom sodium and potassium.
 10. The device of claim 1, wherein the amountof heat generated is proportional to moles of water present at a pointof contact between the alkali metal and the treatment surface.
 11. Thedevice of claim 1, wherein the amount of heat generated is limited bythe amount of or moles of water at a point of contact between the alkalimetal and the treatment surface.
 12. The device of claim 1, wherein theamount of heat generated is proportional to an amount of or moles ofwater at a point of contact between the alkali metal and the treatmentsurface.
 13. The device of claim 1, wherein the alkali metal is neatsodium.
 14. The device of claim 13, wherein the amount of heat generatedis in proportion to moles of water present at a point of contact betweenthe alkali metal and the treatment surface.
 15. The device of claim 1,wherein the alkali metal is an alloy of sodium or an alloy of potassium.16. The device of claim 15, wherein the alkali metal is asodium/potassium alloy.
 17. The device of claim 1, wherein the substrateis a paste.
 18. The device of claim 17, wherein the paste is comprisedof an anhydrous aluminum.
 19. The device of claim 1, wherein thesubstrate is a metal substrate or metal alloy substrate.
 20. The deviceof claim 19, wherein the metal substrate is a stainless steel mesh. 21.The device of claim 1, wherein the substrate is a woven substrate. 22.The device of claim 1, wherein the substrate has a water impermeablelayer.
 23. The device of claim 1, wherein the neat alkali metal isoxidized by water present at the treatment surface.
 24. A kit,comprising: a device according to claim 1; a wipe comprising a solvent;and instructions for use.
 25. The kit of claim 24, wherein the solventis isopropyl alcohol.
 26. The kit of claim 24, further comprising gauze.27. A medical device, comprising: a substrate having a first surface anda second surface, and an alkali metal embedded in or integral with thesubstrate, wherein the alkali metal is a neat alkali metal selected fromsodium and potassium, and wherein the neat alkali metal is present in anamount sufficient to generate an amount of heat in situ when thesubstrate contacts a treatment surface on a human subject to bring theneat alkali metal in contact with water present at the treatmentsurface.